chr13-30906550-C-G

Variant names:

• chr13-30906550-C-G
• NM_032849.4:c.35C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032849.4(MEDAG):​c.35C>G​(p.Pro12Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P12T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MEDAG NM_032849.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.31
• Publications: 0 publications found

Genes affected

MEDAG (HGNC:25926): (mesenteric estrogen dependent adipogenesis) Predicted to be involved in positive regulation of fat cell differentiation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TEX26-AS1 (HGNC:42784): (TEX26 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33480254).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032849.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEDAG	NM_032849.4	MANE Select	c.35C>G	p.Pro12Arg	missense	Exon 1 of 5	NP_116238.3
	TEX26-AS1	NR_038287.1		n.1438-22490G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEDAG	ENST00000380482.9	TSL:1 MANE Select	c.35C>G	p.Pro12Arg	missense	Exon 1 of 5	ENSP00000369849.4	Q5VYS4-1
	MEDAG	ENST00000904728.1		c.35C>G	p.Pro12Arg	missense	Exon 1 of 5	ENSP00000574787.1
	MEDAG	ENST00000968515.1		c.35C>G	p.Pro12Arg	missense	Exon 1 of 3	ENSP00000638574.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.52	T
M_CAP	Pathogenic	0.39	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	0.90	L
PhyloP100		2.3
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.35
MutPred		0.31		Gain of helix (P = 0.0078)
MVP		0.39
MPC		0.58
ClinPred		1.0	D
GERP RS		5.0
PromoterAI		-0.090	Neutral
Varity_R		0.62
gMVP		0.67
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr13-31480687;